Receptor specific receptors

The second application of the CFTI protocol is the evaluation of the free energy differences between four states of the linear form of the opioid peptide DPDPE in solution. Our primary result is the determination of the free energy differences between the representative stable structures j3c and Pe and the cyclic-like conformer Cyc of linear DPDPE in aqueous solution. These free energy differences, 4.0 kcal/mol between pc and Cyc, and 6.3 kcal/mol between pE and Cyc, reflect the cost of pre-organizing the linear peptide into a conformation conducive for disulfide bond formation. Such a conformational change is a pre-requisite for the chemical reaction of S-S bond formation to proceed. The predicted low population of the cyclic-like structure, which is presumably the biologically active conformer, agrees qualitatively with observed lower potency and different receptor specificity of the linear form relative to the cyclic peptide. 

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

Dmg receptors represent another type of receptor family. The central nervous system (CNS) effects of the anxiolytic, diazepam, and the psychotropic actions of the caimabiaoids and phencycUdine have resulted ia the identification of specific receptors for these molecules. This has resulted ia the search for an endogenous ligand for these receptors. Thus, ia these situations, the pharmacological action has preceded the discovery of the receptor which, ia turn, has provided clues ia several iastances to the endogenous ligand. 

Olfactory receptors have been a subject of great interest (9). Much that has been postulated was done by analogy to the sense of sight in which there are a limited number of receptor types and, as a consequence, only three primary colors. Thus attempts have been made to recognize primary odors that can combine to produce all of the odors that can be perceived. Evidence for this includes rough correlations of odors with chemical stmctural types and the existence in some individuals having specific anosmias. Cross-adaptation studies, in which exposure to one odorant temporarily reduces the perception of a chemically related one, also fit into this hypothetical framework. Implicit in this theory is the idea that there is a small number of well-defined odor receptors, so that eventually the shape and charge distribution of a specific receptor can be learned and the kinds of molecular stmctures for a specified odor can be deduced. 

Biochemically, most quaternary ammonium compounds function as receptor-specific mediators. Because of their hydrophilic nature, small molecule quaternaries caimot penetrate the alkyl region of bdayer membranes and must activate receptors located at the cell surface. Quaternary ammonium compounds also function biochemically as messengers, which are generated at the inner surface of a plasma membrane or in a cytoplasm in response to a signal. They may also be transferred through the membrane by an active transport system. 

Adenosine, 6-amino-9-P-ribofuranosyl-9-ff-purine (see Table 1), is an endogenous nucleoside found in all ceUs of the body. Its ubiquitousness suggests that adenosine functions as an autocoid and that its actions are mediated by specific receptors on the plasma membranes of all ceUs. 

Calcium Channel Blockers. Because accumulation of calcium is one of the facets of the mote involved process leading to atherosclerosis, it would foUow that the antihypertensive calcium channel blockers might be effective in preventing atheroma. Both verapamil (Table 1) and nifedipine (Table 3) have been shown to stimulate the low density Upoprotein (LDL) receptor (159). This specific receptor-mediated pathway could theoretically improve Upid metaboUsm in the arterial wall, and thereby prove antiatherogenic. These effects have been proven in animals. 

Oestrogen action is mediated through specific receptors localised within the nucleus of target cells (see Carson-Jurnica et and Tsai and O Malley " for... 

In its simplest form, a model requires two types of data inputs information on the source or sources including pollutant emission rate, and meteorological data such as wind velocity and turbulence. The model then simulates mathematically the pollutant s transport and dispersion, and perhaps its chemical and physical transformations and removal processes. The model output is air pollutant concentration for a particular time period, usually at specific receptor locations. 

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

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